Determination of patient blood volume at start of a dialysis treatment

ABSTRACT

Embodiments of the disclosure provide a method for determining beginning blood volume of a patient during dialysis (e.g., hemodialysis). Ultrafiltration rates are determined at different time stamps during dialysis by obtaining a blood flowrate measurement and hematocrit measurements at input port and output port of a dialyzer connected to the patient. The flowrate and hematocrit measurements are used to determine fluid removed from the patient during dialysis. The ultrafiltration rates and fluid removed from the patient are used to determine the beginning blood volume of the patient.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/207,980, filed on Dec. 3, 2018, which is hereby incorporated byreference in its entirety.

BACKGROUND

Patients with kidney failure or partial kidney failure typically undergohemodialysis treatment, often at a hemodialysis treatment center orclinic. When healthy, kidneys maintain the body's internal equilibriumof water and minerals (e.g., sodium, potassium, chloride, calcium,phosphorous, magnesium, and sulfate). The kidneys also function as partof the endocrine system to produce the hormone erythropoietin as well asother hormones. Hemodialysis is an imperfect treatment to replace kidneyfunction, in part, because it does not correct the endocrine functionsof the kidney. Conventional methods of performing dialysis are based onestimates of the amount of fluid which can be removed from a patientbased on the patient's weight at the time of arrival for regulartreatments. Rough estimates for a “target” weight are determined byalgorithms using factors such as height, weight and other physiologicalconditions before a physician orders the dialysis treatment.

In hemodialysis, blood is taken from a patient through an intake needle(or catheter) which draws blood from an artery located in a specificaccepted access location (arm, thigh, subclavian, etc.). The drawn bloodis pumped through extracorporeal tubing via a peristaltic pump, and thenthrough a special filter termed a “dialyzer.” The dialyzer is intendedto remove unwanted toxins such as blood urea, nitrogen, potassium, andexcess water from the blood. As the blood passes through the dialyzer,it travels in straw-like tubes which serve as semi-permeable membranepassageways for the uncleaned blood. Fresh dialysate liquid, which is asolution of chemicals and water, flows through the dialyzer in thedirection opposite the blood flow. As the dialysate flows through thedialyzer, it surrounds the straw-like membranes in the dialyzer. Thesemembranes feature small holes which are large enough to pass liquid andliquid based impurities—but are not large enough to pass red bloodcells. The fresh dialysate collects excess impurities passing throughthe straw-like tubes by diffusion, and also collects excess waterthrough an ultrafiltration process due to a pressure drop across themembranes. During this process, the red cell volume is preserved insidethe straw-like tubes and recirculated back into the body. The useddialysate exits the dialyzer with the excess fluids and toxins via anoutput tube, thus cleansing the blood and red cell volume flowingthrough the dialyzer. The dialyzed blood then flows out of the dialyzervia tubing and a needle (or catheter) back into the patient. Sometimes,a heparin drip or pump is provided along the extracorporeal blood flowloop in order to prevent red cell clotting during the hemodialysisprocess. Several liters of excess fluid can be removed during a typicalmulti-hour treatment session. In the U.S., a chronic patient willnormally undergo hemodialysis treatment in a dialysis center three timesper week, either on Monday-Wednesday-Friday schedule or aTuesday-Thursday-Saturday schedule. These in-center treatments aretypically completed over 3 to 4 hours with blood flow rates typicallyabove 300 ml/minute. In other countries, the flow rates and time fortreatment are lower and longer, respectively.

Hemodialysis has an acute impact on the fluid balance of the body due inpart to the rapid change in circulating blood volume. When the dialysisfluid removal rate is more rapid than the plasma refilling rate of thestored plasma held by the internal tissue of the body, intravascularblood volume decreases. The resulting imbalance has been linked tocomplications similar to conventional blood loss such as hypotension,loss of consciousness, headaches, vomiting, dizziness and crampsexperienced by the patient, both during and after dialysis treatments.Continuous quantitative measurement of parameters relating to theprocessing of the blood volume (in real-time) during hemodialysis canreduce the chance of dialysis-induced hypotension, and otherwiseoptimize dialysis therapy regimens by controlling fluid balance andaiding in achieving the target dry weight for the patient.

Although dialysis involves fluid removal from a patient, there is noconvenient way of obtaining an initial blood volume of the patientbefore treatment. A patient can go to a hospital or an in-patientfacility to measure blood volume using dilution indicators. For example,a chemical sample is injected into the patient's blood and then a sampleof the blood is extracted to determine concentration of the chemicalsample in the blood using special equipment. Since dialysis clinicsusually do not have a setup for using dilution indicators, blood volumeobtained in this manner may be unhelpful because blood volume is amoving target. That is, before getting to a dialysis clinic, a patientthat measured his blood volume beforehand may have lost blood volumefrom exercising or may have gained blood volume from eating lunch. Thus,the blood volume measurement obtained before reaching the dialysisclinic can be drastically different from the patient's actual bloodvolume at start of dialysis.

SUMMARY

An embodiment of the disclosure provides a system for determiningbeginning blood volume of a patient undergoing dialysis treatment. Thesystem comprises: a first portion of tubing, configured to connect apatient to an input of a dialyzer; a second portion of tubing,configured to connect the patient to an output of the dialyzer; a pump,configured to pump blood from the patient through the first portion oftubing into the dialyzer, and out of the dialyzer into the secondportion of tubing; a first blood chamber, disposed along the firstportion of tubing, and a second blood chamber, disposed along the secondportion of tubing, wherein the first blood chamber and the second bloodchamber are configured to facilitate hematocrit measurement; and acontroller, configured to determine the beginning blood volume usinghematocrit values associated with the input of the dialyzer, hematocritvalues associated with the output of the dialyzer, and a flowrate ofblood through the first portion of tubing.

An embodiment of the disclosure provides a method for determiningbeginning blood volume of a patient connected to a dialysis system. Themethod comprises: circulating, using a pump of the dialysis system,blood from the patient through a dialyzer; and determining, using thedialysis system, beginning blood volume of the patient. Determining thebeginning blood volume includes: (a) determining a blood flowratecorresponding to an input side of the dialyzer; (b) determining a fluidremoval rate at an initial time via the blood flowrate, hematocritcorresponding to the input side of the dialyzer at the initial time andhematocrit corresponding to the output side of the dialyzer at theinitial time; (c) determining a fluid removal rate after a firstmeasurement period via the blood flowrate, hematocrit corresponding tothe input side of the dialyzer after the first measurement period andhematocrit corresponding to the output side of the dialyzer after thefirst measurement period; (d) determining volume of fluid removed forthe first measurement period via the fluid removal rate at the initialtime and the fluid removal rate after the first measurement period; (e)determining fractional blood volume change via hematocrit correspondingto the input side of the dialyzer at the initial time and hematocritcorresponding to the input side of the dialyzer after the firstmeasurement period; and (f) determining the beginning blood volume viathe fractional blood volume change and the volume of fluid removed forthe first measurement period.

An embodiment of the disclosure provides a non-transitory computerreadable medium for determining beginning blood volume of a patientconnected to a dialysis system. The non-transitory computer readablemedium includes instructions for causing a processor of the dialysissystem to facilitate performing: blood circulation, using a pump of thedialysis system, blood from the patient through a dialyzer; anddetermining, using the dialysis system, beginning blood volume of thepatient. Determining the beginning blood volume includes: (a)determining a blood flowrate corresponding to an input side of thedialyzer; (b) determining a fluid removal rate at an initial time viathe blood flowrate, hematocrit corresponding to the input side of thedialyzer at the initial time and hematocrit corresponding to the outputside of the dialyzer at the initial time; (c) determining a fluidremoval rate after a first measurement period via the blood flowrate,hematocrit corresponding to the input side of the dialyzer after thefirst measurement period and hematocrit corresponding to the output sideof the dialyzer after the first measurement period; (d) determiningvolume of fluid removed for the first measurement period via the fluidremoval rate at the initial time and the fluid removal rate after thefirst measurement period; (e) determining fractional blood volume changevia hematocrit corresponding to the input side of the dialyzer at theinitial time and hematocrit corresponding to the input side of thedialyzer after the first measurement period; and (f) determining thebeginning blood volume via the fractional blood volume change and thevolume of fluid removed for the first measurement period.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a typical patient undergoinghemodialysis treatment with a non-invasive, optical blood monitormonitoring the patient's blood in real-time as it passes throughextracorporeal tubing in the hemodialysis system;

FIG. 2 illustrates an exemplary system for determining patient bloodvolume according to some embodiments of the disclosure;

FIG. 3 illustrates a view of a patient undergoing hemodialysis treatmentwith a system configuration that may be used to determine patient bloodvolume according to some embodiments of the disclosure; and

FIG. 4 illustrates a process for determining patient blood volumeaccording to some embodiments of the disclosure.

DETAILED DESCRIPTION

Embodiments of the disclosure provide a non-invasive method fordetermining patient blood volume during dialysis. Knowing a patient'sblood volume at the start of dialysis allows for better, more effectivetreatment of the patient compared to using estimated benchmarks based onweight and height of the patient. The patient's blood volume at thestart of dialysis can be tracked through various treatments to determinehow the blood volume fluctuates over time. Blood volume at start ofdialysis can also inform how long the dialysis treatment should last.

Blood volume at start of a dialysis treatment is a parameter currentlynot available to physicians in dialysis clinics. Thus embodiments of thedisclosure provide a method of benchmarking the condition of dialysispatients at the beginning of their dialysis sessions without resortingto invasive dye and/or isotope methods. Dyes and isotopes are notpractical for use in a dialysis clinic. These systems are not readilyavailable in the clinics and the patients have inadequate time in theclinic based on the time required for dialysis to perform thesemeasurements. In addition, the cost of this type of measurement can beprohibitive and would not be available for every treatment. Yet, due tothe success of a dialysis treatment a patient may feel good after it andeat or drink improperly before the next session. Therefore, theclinician and physician have no readily available benchmark of thepatient's fluid condition at the beginning of a treatment to gauge whatadjustments need to be made in the next session for best fluidmanagement. The embodiments disclosed here provide for the importantbenchmark of the patient's starting fluid level volume. Beforedescribing embodiments of the disclosure, FIG. 1 shows an example setupfor a hemodialysis treatment.

FIG. 1 is a perspective view of an exemplary patient undergoinghemodialysis treatment with a non-invasive, optical blood monitormonitoring the patient's blood in real-time as it passes throughextracorporeal tubing in the hemodialysis system. The environmentillustrated in FIG. 1 is usable with exemplary embodiments of thepresent disclosure. Further, it will be appreciated that the environmentshown in FIG. 1 is merely exemplary, and that the principles discussedherein with respect to exemplary embodiments of the present disclosuremay be implemented in other environments as well.

FIG. 1 illustrates a patient 10 undergoing hemodialysis treatment usinga hemodialysis system 12, as well as a non-invasive, optical bloodmonitor 14. A typical hemodialysis clinic will have several hemodialysissystems 12 for treating patients on a Monday-Wednesday-Friday scheduleor a Tuesday-Thursday-Saturday schedule. While the invention is notlimited to the number of hemodialysis systems located at a clinic, orthe specific type of hemodialysis system, the general operation of thehemodialysis system 12 is helpful for understanding the environment inwhich the invention is intended to operate.

An input needle or catheter 16 is inserted into an access site of thepatient 10, such as in the arm, and is connected to extracorporealtubing 18 that leads to a peristaltic pump 20 and then to a dialyzer orblood filter 22. The dialyzer 22 removes toxins and excess fluid fromthe patient's blood. The dialyzed red cell blood volume is returned fromthe dialyzer 22 through extracorporeal tubing 24 and return needle orcatheter 26. In some parts of the world (primarily the United States),the extracorporeal blood flow may additionally receive a heparin drip toprevent clotting. The excess fluids and toxins are removed by cleandialysate liquid, which is supplied to the dialyzer 22 via tube 28 andremoved for disposal via tube 30. A typical hemodialysis treatmentsession takes about 3 to 5 hours in the United States.

In the exemplary environment depicted in FIG. 1, the optical bloodmonitor 14 includes a blood chamber 32, an optical blood sensor assembly34, and a controller 35. The blood chamber 32 is preferably located inline with the extracorporeal tubing 18 upstream of the dialyzer 22.Blood from the peristaltic pump 20 flows through the tubing 18 into theblood chamber 32. The preferred sensor assembly 34 includes LED photoemitters that emit light optical wavelengths to measure oxyhemoglobin(HbO₂), hemoglobin (Hb), and H₂O. For example, an LED, at substantially810 nm, is isobestic for red blood cell hemoglobin. The blood chamber 32includes lenses so that the emitters and detectors of the sensorassembly 34 can view the blood flowing through the blood chamber 32, anddetermine the patient's real-time hematocrit value using ratiometrictechniques generally known in the prior art.

FIG. 2 illustrates an exemplary system 200 for determining patientbeginning blood volume at start of a dialysis treatment, according tosome embodiments of the disclosure. The system 200 includes a hematocritmeasurement engine 212, a flowrate measurement engine 214, and a bloodvolume engine 216.

The exemplary system 200 shows a generalized embodiment which may beincorporated in the hemodialysis system 12 provided, as outlined inFIGS. 1 and 3. The hematocrit measurement engine 212, the flowratemeasurement engine 214, and the blood volume engine 216 may beimplemented in the hemodialysis system 12 and the non-invasive, opticalblood monitor 14. In this example configuration, the flowratemeasurement engine 214 may be included in the hemodialysis system 12,the hematocrit measurement engine 212 included in the optical bloodmonitor 14, and the blood volume engine 216 included in the opticalblood monitor 14 and/or in the hemodialysis system 12. The hemodialysissystem 12 and the optical blood monitor 14 can be communicably coupledto each other to realize the relationships provided in FIG. 2 for system200, or the desired parameters can be measured independently withdiscrete calculations.

For an integrated embodiment, the hematocrit measurement engine 212, theflowrate measurement engine 214, and the blood volume engine 216correspond to hardware that includes one or more processors, forexample, microprocessors or microcontrollers. The hardware can alsoinclude a non-transitory computer-readable medium for temporary and/orpermanent storage, for example, a read-only memory (ROM), a randomaccess memory (RAM), a flash memory, and other computer memories andstorage. Additionally, the hematocrit measurement engine 212 may utilizeone or more optical blood sensor assemblies, for example, optical bloodsensor assembly 34, to measure hematocrit values at both main blood flowports of the dialyzer 204. The blood volume engine 216 may be acomputing device, for example, the controller 35, that utilizes aprocessor and storage to determine the hematocrit values of the dialyzer204, read the blood flowrate entering the dialyzer 204 from theprocessor in the dialysis machine 12, read the ultra-filtration pumprate of the dialysis machine 12 and then calculate beginning bloodvolume of the patient at the start of dialysis.

In the system 200 of FIG. 2, as applied to FIG. 3, blood flows into aninput port of the dialyzer 204 at a blood flowrate Q_(b). The bloodflowrate is determined by the pump 202, which may be peristaltic pump20, which is part of the dialysis machine 12 of FIG. 3. In the treatmentsetting of FIG. 3, blood enters the dialyzer 204, undergoes a filtrationprocess, and filtered blood flows out of an output port of the dialyzer204 at a blood flowrate Q_(out). The difference between the bloodflowrate at the input port of the dialyzer 204 and the blood flowrate atthe output port of the dialyzer 204 is denoted in FIG. 2 as Q_(UFR). Inthe treatment setting of FIG. 3, the Q_(out) rate is the differencedetermined by the Q_(b) rate minus the Q_(UFR). The pumps on thedialysis machine 12 are calibrated, and these calibrated values arereadily available during measurements. These rates can be arbitrary, butshould remain the same throughout the measurements.

Multiple methods may be used to determine the flowrate Q_(b). As shownin FIG. 2, in one embodiment, a flowmeter 210 is provisioned in theextracorporeal tubing to measure Q_(b). The measurements from theflowmeter 210 may be provided to the flowrate engine 214.

In another exemplary embodiment, the flowmeter 210 may or may not beprovided, and Q_(b) is determined from a calibrated pumping rate of thepump 202. The pump 202 may operate at a specific number of rotations perminute, which may be matched to a commanded flowrate of blood enteringthe dialyzer 204. The pump 202 may provide the number of rotations perminute to the flowrate engine 214, which then determines Q_(b) from thenumber of rotations per minute.

In addition to determining flowrates, the system 200 also determineshematocrit at the input port of the dialyzer 204 (HCT₂₀₆) and the outputport of the dialyzer 204 (HCT₂₀₈). In one embodiment, a ratiometrictechnique, as disclosed in U.S. Pat. No. 5,372,136 entitled, “System andMethod for Non-Invasive Hematocrit Monitoring,” which is incorporated byreference in its entirety, can be used to determine hematocrit values atlocations 206 and 208 in FIG. 2. If one optical blood sensor assembly 34is used, then after measuring hematocrit at the input port of thedialyzer 204 (HCT₂₀₆), the optical blood assembly 34 is moved to measurehematocrit at the output port of the dialyzer 204 (HCT₂₀₈). If twooptical blood sensor assemblies are used, then one can measure HCT₂₀₆while the other measures HCT₂₀₈. In some embodiments, non-invasive (notrequiring the pulling of samples) hematocrit measurements, for example,measurements made with the Crit-Line® system, may be used to obtainhematocrit values.

The blood volume engine 216 receives hematocrit measurements from thehematocrit measurement engine 212 and receives flowrate measurementsfrom the flowrate engine 214. Using the hematocrit and the flowratemeasurements, the blood volume engine 216 determines the total bloodvolume of the patient at the start of the dialysis treatment. The totalblood volume of the patient at the start of dialysis treatment isdetermined by dividing the total blood volume of the patient removedduring a treatment time by a fractional blood volume change during thesame treatment time. The total blood volume removed and the fractionalblood volume change are determined using the measured hematocrit valuesHCT₂₀₆ and HCT₂₀₈ and the blood flow rate Q_(b).

Determination of a patient's total blood volume at time zero (TBV₀), atthe commencement of a dialysis treatment, involves two sets ofmeasurements since there are two unknowns, i.e., TBV₀ and instantaneoustotal blood volume at time T into the treatment, TBV(T). For performingthese measurements, it is assumed that the dialysis access is viable andthere is no recirculation from the venous to the arterial needles due tostenosis in or after the access.

For the first set of measurements, the fractional change in blood volume(ΔBV) measured by a device such as the Crit-Line® or the Crit-Line® clipmonitor (CLiC™) device must be based on calibrated blood parameters. Forexample, the ΔBV must be based on calibrated hematocrit values beingaccurate or traceable to any standard calibrated measurement of thehematocrit blood parameter.

In an embodiment, the measurement of ΔBV can be made using the CLiC™device at location 206. A blood chamber can be placed at 206 tofacilitate the measurement with the CLiC™ device. When the CLiC™ deviceis manufactured, each is measured on a matching blood chamber to verifyaccuracy of hematocrit measurements made by the device through use ofhuman blood in the production facility's blood lab. The CLiC™ device isused here as an example of the hematocrit measurement engine 212. Sincethe hematocrit values measured are equivalent to laboratory hematocritaccuracy, the calibrated state of the device can be used to make aviable measurement of ΔBV at any point in time during a dialysistreatment. Hematocrit (HCT) can be defined as Eq. 1.

$\begin{matrix}{{HCT} = \frac{RBV}{TBV}} & {{Eq}.1}\end{matrix}$

Where HCT is hematocrit, RBV is red blood cell volume, and TBV is totalblood volume. Based on the mass balance condition where no red bloodcell volume is lost in the dialyzer (only fluid is removed from theblood), calculations can be performed based on HCT₂₀₆ measured atlocation 206.

An initial HCT₂₀₆ can be measured at the beginning of treatment (at timeT=0) before being influenced by fluid removal. The initial HCT₂₀₆ isreferred to as HCT₀ from here on to distinguish from subsequent HCT₂₀₆measurements. From Eq. 1, HCT₀ can be written as Eq. 2.

$\begin{matrix}{{HCT_{0}} = \frac{RBV}{TBV_{0}}} & {{Eq}.2}\end{matrix}$

Where HCT₀ is the initial hematocrit HCT₂₀₆ measured at the beginning oftreatment, RBV is red blood cell volume, and TBV₀ is the initial totalblood volume at the beginning of treatment (at time T=0).

At time duration T, a subsequent hematocrit can be measured. HematocritHCT₂₀₆ measured at time duration T can be defined as Eq. 3.

$\begin{matrix}{{HC{T(T)}} = \frac{RBV}{TB{V(T)}}} & {{Eq}.3}\end{matrix}$

Where HCT(T) is the hematocrit HCT₂₀₆ measured at time T into thetreatment, RBV is red blood cell volume, and TBV(T) is total bloodvolume at time T into the treatment.

Eq. 2 and Eq. 3 can be rearranged to produce Eq. 4 and Eq. 5,respectively.

$\begin{matrix}{{TBV_{0}} = \frac{RBV}{HCT_{0}}} & {{Eq}.4}\end{matrix}$ $\begin{matrix}{{{TBV}(T)} = \frac{RBV}{HC{T(T)}}} & {{Eq}.5}\end{matrix}$

Since RBV is constant, Eq. 4 and Eq. 5 can be combined to calculatefractional change in blood volume ΔBV as indicated in Eq. 6.

$\begin{matrix}{{\Delta BV} = {\frac{{TB{V(T)}} - {TBV_{0}}}{TBV_{0}} = \lbrack {\frac{HCT_{0}}{HC{T(T)}} - 1} \rbrack}} & {{Eq}.6}\end{matrix}$

The ΔBV is based on calibrated hematocrit values and is bounded by theaccuracy of the hematocrit measurements. Rearranging Eq. 6 provides Eq.7.

ΔBV×TBV₀=TBV(T)−TBV₀

TBV(T)=TBV₀×(ΔBV+1)  Eq. 7

Eq. 7 provides a relationship for the first set of measurements andprovides a first equation involving two unknowns, both the originalpatient blood volume TBV₀ at the beginning of treatment and the patientblood volume TBV (T) at some time T into the treatment. To solve Eq. 7,a second set of measurements is determined.

The second relationship between TBV₀ and TBV(T) involves an approximateintegration of the blood volume fluid amount removed from time zero(i.e., from time T=0). That is, the total blood removed throughultrafiltration from time zero (e.g., the start of treatment) until timeT can be written as Eq. 8. Eq. 8 presents fluid removal volume based ona sampled integration technique based on timed samples.

$\begin{matrix}{{{TB{V(T)}} - {TBV_{0}}} = {\sum\limits_{n = {1{({{step}\Delta t})}}}^{{T/\Delta}t}{( \frac{{Q_{UFR}(n)} + {Q_{UFR}( {n - 1} )}}{2} ) \times \Delta t}}} & {{Eq}.8}\end{matrix}$

In Eq. 8, Q_(UFR) is actual fluid removal rate in the dialysis circuitbased on ultrafiltration mechanisms. Q_(UFR) is not the ultrafiltrationrate of an ultrafiltration pump. At is time between measurements ofQ_(UFR) along the TBV (T) history curve. The smaller Δt becomes, themore data is processed by the blood volume engine 216 and the moreaccurate the integration estimation of Eq. 8 becomes. Time T is totaltime into the treatment in which Q_(UFR) has been active. For use of Eq.8, ultrafiltration pump rate and blood pump rate should remain atsteady-state from an initial time T=0 until time T. To enhancereadability, the initial time T=0 will be referred to as initial timet₀. In an embodiment, the floor of T/Δt can be seen as number ofmeasurement periods from the initial time t₀.

The Q_(UFR) volume change is the rate of removing fluid from the blood(in the dialyzer 204) into the dialysate. This should not be confusedwith pump ultrafiltration rate value set for an ultrafiltration pump forcirculating dialysate through the dialyzer 204. Because the fluidremoval from the patient's blood is accomplished by osmosis using thedialysate liquid passing through the dialyzer 204, external to thedialyzer fibers, while blood flow is confined within the dialyzerfibers, the actual fluid volume transfer Q_(UFR) is not equal to theflowrate of dialysate (ultrafiltration pump rate) passing outside thedialyzer fibers. The fluid volume transfer is dependent not only on theultrafiltration pump rate but also on factors such as, efficiency of thedialyzer construction, chemistry makeup of the dialysate, and so on. Thefluid volume rate removed from the blood Q_(UFR) is an additivecomponent to the spent dialysate volume as it passes out of thedialyzer.

Solving Eq. 8 for TBV(T) provides Eq. 9, and setting Eq. 7 equal to Eq.9 provides Eq. 10.

$\begin{matrix}{{TB{V(T)}} = {\lbrack {\sum\limits_{n = {1{({{Step}\Delta t})}}}^{{T/\Delta}t}{( \frac{{Q_{UFR}(n)} + {Q_{UFR}( {n - 1} )}}{2} ) \times \Delta t}} \rbrack + {TBV_{0}}}} & {{Eq}.9}\end{matrix}$ $\begin{matrix}{{{TB}V_{0}} = \frac{\lbrack {\sum_{n = {1{({{Step}\Delta t})}}}^{{T/\Delta}t}{( \frac{{Q_{UFR}(n)} + {Q_{UFR}( {n - 1} )}}{2} ) \times \Delta t}} \rbrack}{\Delta BV}} & {{Eq}.10}\end{matrix}$

Thus, to determine an accurate TBV₀ by solving Eq. 10, actual Q_(UFR)must be determined. Q_(UFR) can be measured from the following outlinedprocess:

Dialysis blood pump is calibrated and accurate in its settings formoving blood through the dialyzer blood circuit. That is, pump 202should provide a calibrated pump volume flow Q_(b). Commonly, pumps usedin dialysis are calibrated at their factories.

During the measurement period, pump volume flow Q_(b) should remainconstant from time t₀ to time T.

Calibrated hematocrit sensors, e.g., Crit-Line® or CLiC™ devices, areused to measure HCT₂₀₆ and HCT₂₀₈. As previously discussed, one sensorcan be used measure HCT₂₀₆ and afterwards used to measure HCT₂₀₈ for asetup in FIG. 1, or two sensors can be used to simultaneously measureboth HCT₂₀₆ and HCT₂₀₈ for a setup in FIG. 3. Δt can be used to gaugewhether one sensor or two sensors will suffice. If Δt is reasonablylarge, e.g., 1 sample per minute or more, a single sensor can be used tomeasure hematocrit at both points because dialysis parameters do notchange quickly.

At a periodic time interval Lit, with the dialysis pump set to aconstant and known Q_(b), HCT₂₀₆ and HCT₂₀₈ are measured simultaneously(or near simultaneously if the hematocrit values are not changingrapidly). At the same time hematocrit measurements are made, fractionalchange in blood volume ΔBV is calculated using Eq. 6 and HCT₂₀₆.

Using mass balance of the red blood cell volume flowing through thedialyzer (assuming no loss of red blood cell volume during time T), thefollowing relationships can be derived to solve for Q_(UFR). Beginningat location 206:

$\begin{matrix}{{HCT_{206}} = \frac{RBVR}{Q_{b}}} & {{Eq}.11}\end{matrix}$

Where HCT₂₀₆ is calibrated measured hematocrit at location 206, RBVR isred blood cell volume rate flowing through the dialyzer, and Q_(b) isblood flow rate dictated by a calibrated blood pump. A similarrelationship can be written at location 208 as:

$\begin{matrix}{{HCT_{208}} = \frac{RBVR}{Q_{b} - Q_{UFR}}} & {{Eq}.12}\end{matrix}$

Where HCT₂₀₈ is calibrated measured hematocrit at location 208, RBVR isred blood cell volume rate flowing through the dialyzer, Q_(b) iscalibrated blood flowrate, and Q_(UFR) is true fluid removal volumerate.

Embodiments of the disclosure use the hematocrit monitoring engine 212to measure the hematocrit of the blood entering the dialyzer 204 andthen the HCT blood exiting the dialyzer 204. Due to the nature of thedialyzer 204, no red blood cells are lost across dialyzer membraneswithin the dialyzer 204—only fluid, for example, urea, passes throughinto the waste collecting dialysate. Since red blood cells do not crossthe dialyzer membranes into the waste, mass balance analysis of the redblood cell volume is applicable. Assuming red blood cell volume isconstant (i.e., no red blood cell volume is lost during time T), thenEqs. 11 and 12 can be combined to provide Eq. 13:

HCT₂₀₆ ×Q _(b)=HCT₂₀₈×(Q _(b) −Q _(UFR))  Eq. 13

Eq. 13 can be rearranged as Eq. 14.

$\begin{matrix}{{QUFR} = {( \frac{{HCT_{208}} - {HCT_{206}}}{HCT_{208}} ) \times Q_{b}}} & {{Eq}.14}\end{matrix}$

Since HCT₂₀₈ and HCT₂₀₆ are calibrated hematocrit values and Q_(b) is acalibrated flow rate of the blood pump 202, Q_(UFR), which is derivedfrom the calibrated values of HCT₂₀₈, HCT₂₀₆, and Q_(b), is also acalibrated value. Values of Q_(UFR) obtained and used at samples n=0through n=[T/Δt] with sampling rate of Lit, can be used in Eq. 10 tocalculate a number of solutions for TBV₀. Successive values ofcalculated TBV₀ at each measurement time nΔt can be averaged to improveaccuracy of TBV₀ obtained.

The blood volume engine 216 determines TBV₀ using relationships shown inEq. 10 and Eq. 14, depending on information received from the hematocritmeasurement engine 212 and the flowrate engine 214. Note that in FIG. 2,dotted lines represent potential alternative inputs for determiningflowrate, some or all of which may be used in different exemplaryembodiments. For example, the blood flowrate at the input of thedialyzer 204 is desired, but this flowrate can be determined from eitherthe calibrated pump 202 or the flowmeter 210, thus one of thesemeasurement paths may be active and the other inactive.

FIG. 4 illustrates a process 400 for determining patient blood volume,according to some embodiments of the disclosure. At step 402, the system200 determines Q_(UFR) (actual fluid removal rate) at an initial time t₀using Q_(b) (calibrated blood flowrate) and hematocrit measurementsHCT₂₀₆ and HCT₂₀₈ at the time t₀. The blood volume engine 216 determinesQ_(UFR) at time t₀ according to Eq. 14 using HCT₂₀₆ and HCT₂₀₈ at thetime t₀ from the hematocrit measurement engine 212 and Q_(b) from theflowrate engine 214. The Q_(UFR) measured is associated with time t₀,and a temporary variable i=└T/Δt┘ is used to keep track of total numberof measurement periods, a current or most recent measurement period, ora total number of TBV₀ measurements taken. Initially, at time T=0, i is0, and i only becomes 1 after a time period Δt has passed. That is, onceT reaches Δt.

At step 404, after an elapsed time Δt, the blood volume engine 216automatically increments i, based on the mathematical relationshipabove, and determines Q_(UFR) in a similar manner as already discussedwith respect to step 402. The Q_(UFR) determined at 404 is Q_(UFR) forthe measurement period i.

At step 406, the blood volume engine 216 determines difference in totalblood volume for cumulative measurement periods between time t₀ (T=0)and time T. That is, the blood volume engine 216 determines fluidremoved during a total number of elapsed measurement periods in the timeT. Referring to Eq. 8, volume removed during a single measurement periodinvolves adding a previous Q_(UFR) and a current Q_(UFR), dividing theresult of the addition by 2, and then multiplying the result by theduration Δt between the Q_(UFR) measurements. That is, volume removed inmeasurement period i is determined using Q_(UFR) for measurement periodi−1, Q_(UFR) for measurement period i, and Δt, time duration betweenQ_(UFR) measurements for periods i−1 and i. The volume removed inmeasurement period i is then added to total volume removed from time t₀until measurement period i−1 to obtain total blood volume removed forcumulative measurement periods between time t₀ and T.

For illustrative purposes, an example is provided. At time t₀, totalvolume removed is 0. At measurement period 1, volume removed iscalculated to be TBV(1Δt)−TBV₀. This value, TBV(1Δt)−TBV₀, is added tothe previous total volume removed, 0, to obtain current total volumeremoved, TBV (1Δt)−TBV₀. At measurement period 2, volume removed iscalculated to be TBV (2Δt)−TBV (1Δt). This value, TBV (2Δt)−TBV (1Δt),is added to the previous total volume removed, TBV (1Δt)−TBV₀, to obtainthe current total volume removed TBV (2Δt)−TBV₀. In this manner, throughevery successive measurement period, a difference of volume removed fora most recent measurement period is continually calculated and added toa running total of blood volume removed. At 406, the blood volume engine216 thus determines fluid removed for cumulative measurement periodsfrom initial time t₀ until a most recent time T.

At step 408, the blood volume engine 216 determines percentage change inblood volume or fractional change in blood volume ΔBV for the cumulativemeasurement periods. The ΔBV is determined according to Eq. 6, with HCT₀being HCT₂₀₆ at initial time t₀ and HCT(T) being HCT₂₀₆ for the mostrecent measurement period i. Since measurements are made at sampleintervals Δt, note that HCT(T) for the most recent measurement period icorresponds to HCT(iΔt).

At step 410, the blood volume engine 216 determines and stores TBV₀solution for the current measurement period i. The blood volume engine216 determines the beginning blood volume of the patient TBV₀, asdefined in Eq. 10, using the ΔBV from step 408 and the difference intotal blood volume from step 406.

At step 412, the blood volume engine 216 displays stored TBV₀ formeasurement period i and current time T and/or time when the measurementwas taken iΔt.

At step 414, the blood volume engine 216 determines whether there aremore measurement periods. If there are more measurements to be made,then a new Q_(UFR) measurement is made at step 404 and i is incremented,otherwise the blood volume engine 216 determines, at step 416, anaverage of the stored TBV₀ solutions for measurement period 1 throughmeasurement period i.

At step 418, the blood volume engine 216 displays data summary of allmeasurements made during the process 400.

Based on the value that a user obtains from the output of thehemodialysis system 12, the user may determine a treatment plan for thepatient or know how aggressive the dialysis treatment should be. If thepatient's beginning blood volume differs significantly from previousvisits, the user (physician) can further provide additional tips to thepatient on managing the total blood volume.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

The use of the terms “a” and “an” and “the” and “at least one” andsimilar referents in the context of describing the invention (especiallyin the context of the following claims) are to be construed to coverboth the singular and the plural, unless otherwise indicated herein orclearly contradicted by context. The use of the term “at least one”followed by a list of one or more items (for example, “at least one of Aand B”) is to be construed to mean one item selected from the listeditems (A or B) or any combination of two or more of the listed items (Aand B), unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. Recitation of ranges of valuesherein are merely intended to serve as a shorthand method of referringindividually to each separate value falling within the range, unlessotherwise indicated herein, and each separate value is incorporated intothe specification as if it were individually recited herein. All methodsdescribed herein can be performed in any suitable order unless otherwiseindicated herein or otherwise clearly contradicted by context. The useof any and all examples, or exemplary language (e.g., “such as”)provided herein, is intended merely to better illuminate the inventionand does not pose a limitation on the scope of the invention unlessotherwise claimed. No language in the specification should be construedas indicating any non-claimed element as essential to the practice ofthe invention.

Preferred embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention.Variations of those preferred embodiments may become apparent to thoseof ordinary skill in the art upon reading the foregoing description. Theinventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

1. A method for determining beginning blood volume of a patientconnected to a dialysis system, the method comprising: circulating,using a pump of the dialysis system, blood from the patient through adialyzer; and based on circulating the blood from the patient throughthe dialyzer, determining, using the dialysis system, the beginningblood volume of the patient using hematocrit values associated with aninput side of the dialyzer, hematocrit values associated with an outputside of the dialyzer, and a flowrate of blood through a first portion oftubing connecting the patient to the input of the dialyzer.
 2. Themethod according to claim 1, wherein determining the beginning bloodvolume further includes: displaying the beginning blood volume on ascreen of the dialysis system.
 3. The method according to claim 1,wherein the flowrate of blood corresponding to the input side of thedialyzer is determined via a calibrated pumping rate of the pump or aninput flowmeter of the dialysis system.
 4. The method of claim 1,wherein the hematocrit values associated with the input side of thedialyzer comprise hematocrit corresponding to the input side of thedialyzer at an initial time and hematocrit corresponding to the inputside of the dialyzer after a first measurement period, wherein thehematocrit values associated with the output side of the dialyzercomprise hematocrit corresponding to the output side of the dialyzer atthe initial time and hematocrit corresponding to the output side of thedialyzer after the first measurement period.
 5. The method according toclaim 4, wherein hematocrit corresponding to the input side of thedialyzer and hematocrit corresponding to the output side of the dialyzerare measured via a first sensor assembly of the dialysis system and asecond sensor assembly of the dialysis system, respectfully.
 6. Themethod according to claim 4, wherein hematocrit corresponding to theinput side of the dialyzer is measured via a sensor assembly of thedialysis system, and after a time period, hematocrit corresponding tothe output side of the dialyzer is measured via the sensor assembly ofthe dialysis system.
 7. The method of claim 4, wherein determining thebeginning blood volume of the patient comprises: determining theflowrate of blood corresponding to the input side of the dialyzer;determining a fluid removal rate at the initial time via the flowrate ofblood, the hematocrit corresponding to the input side of the dialyzer atthe initial time and the hematocrit corresponding to the output side ofthe dialyzer at the initial time; determining a fluid removal rate afterthe first measurement period via the flowrate of blood, the hematocritcorresponding to the input side of the dialyzer after the firstmeasurement period and the hematocrit corresponding to the output sideof the dialyzer after the first measurement period; determining volumeof fluid removed for the first measurement period via the fluid removalrate at the initial time and the fluid removal rate after the firstmeasurement period; determining fractional blood volume change via thehematocrit corresponding to the input side of the dialyzer at theinitial time and the hematocrit corresponding to the input side of thedialyzer after the first measurement period; and determining thebeginning blood volume via the fractional blood volume change and thevolume of fluid removed for the first measurement period.
 8. The methodaccording to claim 7, wherein determining the beginning blood volumefurther includes: determining whether there are more measurementperiods; and in response to the determining that there are moremeasurement periods, performing using the dialysis system: determining afluid removal rate for a next measurement period via the flowrate ofblood, hematocrit corresponding to the input side of the dialyzer afterthe next measurement period and hematocrit corresponding to the outputside of the dialyzer after the next measurement period; determiningcumulative volume of fluid removed via two most recent fluid removalrates determined and volume of fluid removed for a previous measurementperiod; determining the fractional blood volume change via thehematocrit corresponding to the input side of the dialyzer at theinitial time and the hematocrit corresponding to the input side of thedialyzer for the next measurement period; and determining the beginningblood volume via the fractional blood volume change and the cumulativevolume of fluid removed.
 9. The method according to claim 8, wherein inresponse to the determining that there are more measurement periods, thedialysis system further performs: determining average beginning bloodvolume for all measurement periods; and displaying the average of themultiple beginning blood volumes on a screen of the dialysis system. 10.The method according to claim 8, wherein each measurement period has aduration of 1 minute.
 11. A non-transitory computer readable mediumhaving processor-executable instructions stored thereon for determiningbeginning blood volume of a patient connected to a dialysis system,wherein the processor-executable instructions, when executed,facilitate: circulating, using a pump of the dialysis system, blood fromthe patient through a dialyzer; and based on circulating the blood fromthe patient through the dialyzer, determining, using the dialysissystem, the beginning blood volume of the patient using hematocritvalues associated with an input side of the dialyzer, hematocrit valuesassociated with an output side of the dialyzer, and a flowrate of bloodthrough a first portion of tubing connecting the patient to the input ofthe dialyzer.
 12. The non-transitory computer readable medium accordingto claim 11, wherein determining the beginning blood volume furtherincludes: displaying the beginning blood volume on a screen of thedialysis system.
 13. The non-transitory computer readable mediumaccording to claim 11, wherein the hematocrit values associated with theinput side of the dialyzer comprises hematocrit corresponding to theinput side of the dialyzer at an initial time and hematocritcorresponding to the input side of the dialyzer after a firstmeasurement period, wherein the hematocrit values associated with theoutput side of the dialyzer comprises hematocrit corresponding to theoutput side of the dialyzer at the initial time and hematocritcorresponding to the output side of the dialyzer after the firstmeasurement period.
 14. The non-transitory computer readable mediumaccording to claim 13, wherein determining the beginning blood volume ofthe patient comprises: determining the flowrate of blood correspondingto the input side of the dialyzer; determining a fluid removal rate atthe initial time via the flowrate of blood, the hematocrit correspondingto the input side of the dialyzer at the initial time and the hematocritcorresponding to the output side of the dialyzer at the initial time;determining a fluid removal rate after the first measurement period viathe flowrate of blood, the hematocrit corresponding to the input side ofthe dialyzer after the first measurement period and the hematocritcorresponding to the output side of the dialyzer after the firstmeasurement period; determining volume of fluid removed for the firstmeasurement period via the fluid removal rate at the initial time andthe fluid removal rate after the first measurement period; determiningfractional blood volume change via the hematocrit corresponding to theinput side of the dialyzer at the initial time and the hematocritcorresponding to the input side of the dialyzer after the firstmeasurement period; and determining the beginning blood volume via thefractional blood volume change and the volume of fluid removed for thefirst measurement period.
 15. The non-transitory computer readablemedium according to claim 13, wherein determining the beginning bloodvolume further includes: determining whether there are more measurementperiods; and in response to the determining that there are moremeasurement periods, performing using the dialysis system: determining afluid removal rate for a next measurement period via the flowrate ofblood, hematocrit corresponding to the input side of the dialyzer afterthe next measurement period and hematocrit corresponding to the outputside of the dialyzer after the next measurement period; determiningcumulative volume of fluid removed via two most recent fluid removalrates determined and volume of fluid removed for a previous measurementperiod; determining the fractional blood volume change via thehematocrit corresponding to the input side of the dialyzer at theinitial time and the hematocrit corresponding to the input side of thedialyzer for the next measurement period; and determining the beginningblood volume via the fractional blood volume change and the cumulativevolume of fluid removed.
 16. The non-transitory computer readable mediumaccording to claim 15, wherein in response to the determining that thereare more measurement periods, the dialysis system further performs:determining average beginning blood volume for all measurement periods;and displaying the average of the multiple beginning blood volumes on ascreen of the dialysis system.
 17. An apparatus for determiningbeginning blood volume of a patient connected to a dialysis system, theapparatus comprising: a processor; and a memory havingprocessor-executable instructions stored thereon, wherein theprocessor-executable instructions, when executed by the processor,facilitate: circulating, using a pump of the dialysis system, blood fromthe patient through a dialyzer; and based on circulating the blood fromthe patient through the dialyzer, determining, using the dialysissystem, the beginning blood volume of the patient using hematocritvalues associated with an input side of the dialyzer, hematocrit valuesassociated with an output side of the dialyzer, and a flowrate of bloodthrough a first portion of tubing connecting the patient to the input ofthe dialyzer.
 18. The apparatus of claim 17, wherein determining thebeginning blood volume further includes: displaying the beginning bloodvolume on a screen of the dialysis system.
 19. The apparatus of claim17, wherein the flowrate of blood corresponding to the input side of thedialyzer is determined via a calibrated pumping rate of the pump or aninput flowmeter of the dialysis system.
 20. The apparatus of claim 17,wherein the hematocrit values associated with the input side of thedialyzer comprises hematocrit corresponding to the input side of thedialyzer at an initial time and hematocrit corresponding to the inputside of the dialyzer after a first measurement period, wherein thehematocrit values associated with the output side of the dialyzercomprises hematocrit corresponding to the output side of the dialyzer atthe initial time and hematocrit corresponding to the output side of thedialyzer after the first measurement period.
 21. The apparatus of claim20, wherein determining the beginning blood volume of the patientcomprises: determining the flowrate of blood corresponding to the inputside of the dialyzer; determining a fluid removal rate at the initialtime via the flowrate of blood, the hematocrit corresponding to theinput side of the dialyzer at the initial time and the hematocritcorresponding to the output side of the dialyzer at the initial time;determining a fluid removal rate after the first measurement period viathe flowrate of blood, the hematocrit corresponding to the input side ofthe dialyzer after the first measurement period and the hematocritcorresponding to the output side of the dialyzer after the firstmeasurement period; determining volume of fluid removed for the firstmeasurement period via the fluid removal rate at the initial time andthe fluid removal rate after the first measurement period; determiningfractional blood volume change via the hematocrit corresponding to theinput side of the dialyzer at the initial time and the hematocritcorresponding to the input side of the dialyzer after the firstmeasurement period; and determining the beginning blood volume via thefractional blood volume change and the volume of fluid removed for thefirst measurement period.
 22. The apparatus of claim 21, whereindetermining the beginning blood volume further includes: determiningwhether there are more measurement periods; and in response to thedetermining that there are more measurement periods, performing usingthe dialysis system: determining a fluid removal rate for a nextmeasurement period via the flowrate of blood, hematocrit correspondingto the input side of the dialyzer after the next measurement period andhematocrit corresponding to the output side of the dialyzer after thenext measurement period; determining cumulative volume of fluid removedvia two most recent fluid removal rates determined and volume of fluidremoved for a previous measurement period; determining the fractionalblood volume change via the hematocrit corresponding to the input sideof the dialyzer at the initial time and the hematocrit corresponding tothe input side of the dialyzer for the next measurement period; anddetermining the beginning blood volume via the fractional blood volumechange and the cumulative volume of fluid removed.
 23. The apparatus ofclaim 22, wherein in response to the determining that there are moremeasurement periods, the dialysis system further performs: determiningaverage beginning blood volume for all measurement periods; anddisplaying the average of the multiple beginning blood volumes on ascreen of the dialysis system.